Cannabinoid is a general term for marijuana components contained in cannabis. So far, about 60 kinds or more of the components are known, which mainly include tetrahydrocannabinol, cannabinol, cannabidiol, and the like. Marijuana has been used for thousands of years for medicines or the like, induces psychological and neural reactions, and causes sensory confusion, euphoria, analgesic action, hallucination, and the like. Cannabinoids have various types of pharmacological actions and have been found to have immunosuppressive action, anti-inflammatory action, analgesic action, and the like in addition to the action on the central nervous system.
A cannabinoid is a seven transmembrane G-protein coupled receptor, and so far, two types including cannabinoid receptors type 1 (CB1) and type 2 (CB2) have been identified and screened (Nature, 1990, 346, 561-564; Nature, 1993, 365, 61-65). Human CB1 is constituted with 472 amino acids, and highly expressed in the pallidum, corpus striatum, substantia nigra, hippocampus, the cerebellar molecular layer, the cerebral cortex, and the like in the brain. CB1 is also expressed in the testes, the deferent duct, the uterus, the small intestine, blood vessels, and the like, in addition to the brain. CB2 is constituted with 360 amino acids and exhibits 44% homology with CB1. CB2 is highly expressed in the spleen, the tonsils, and lymph nodes and further in leukocytic cells such as macrophages, monocytes, B-lymphocytes, NK cells, eosionophills and the like. Recently, it has been reported that CB2 is also expressed in the brain (Science, 2005, 310, 329-332).
A CB2 agonist has been reported to exhibit central analgesic action (European Journal of Neuroscience, 2006, 23, 1530-1538) and peripheral analgesic action (Proceedings of the National Academy of Sciences, 2005, 102, 3093-3098). In addition, it has been reported that since CB2 is highly expressed in hematocytes and immunocytes, a CB2 agonist exhibits immunosuppressive action and anti-inflammatory action (British Journal of Pharmacology, 2003, 139, 775-786). The CB2 agonist has been reported to have an antipruritic action in skin diseases (Science, 2007, 316, 1494-1497), and is expected to be applied to atopic dermatitis and the like. Moreover, due to its anti-inflammatory action and immunosuppressive action, the CB2 agonist is expected to be effective for atherosclerosis (Nature, 2005, 434, 782-786), reflux esophagitis (European Journal of Pharmacology, 2007, 573, 206-213), hepatic disorder (British Journal of Pharmacology, 2008, 153, 286-289), and chronic liver diseases (Expert Opinion of Therapeutic Targets, 2007, 11, 403-409). Furthermore, it has been reported that CB2 is also expressed in osteoblasts and osteoclasts, and that a CB2 agonist has an action of increasing the activity of osteoblasts and inhibiting the activity of the osteoclasts, thereby having an action of inhibiting osteoclasia (Proceedings of the National Academy of Sciences, 2006, 103, 696-701).
As compounds having CB2 agonist action, for example, the compounds represented by the following Formula (A) (Patent Document 1), Formula (B) (Patent Document 2), Formula (C) (Patent Documents 3 and 4), Formula (D) (Non-Patent Document 1), and Formula (E) (Patent Document 5) have been reported respectively. However, none of the above documents includes the disclosure or implication about a compound of Formula (I) described later or a salt thereof according to the present invention,

(in the Formulae (A) and (B), X1 particularly represents NR12; X2 and X3 represent a —CR13═CR11— group in combination, or X3 represents NR12; X1 and X2 represent a —CR13═CR11— group in combination, see the corresponding gazettes for detail, see the corresponding gazette for Formula (C), and see the corresponding gazette for Formula (D), in Formula (E), R6 represents methyl, chloro, or CHxFn, see the corresponding gazette for detail).